Group A rotaviruses (RV) are the major etiologic agents of severe dehydrating diarrhea in children under 5 years age, leading to 870, 000 deaths annually in the developing world. One potential cause of virus-related adverse reactions is due to the interaction of certain host proteins with the viral nonstructural proteins and/or nucleic acids. Often the outcome of virus-host interaction determines the viral pathogenesis, persistence and host range. RV has the ability to establish persistent infection like the other members of reovirus family and orbiviruses. In addition, one of the viral nonstructural proteins, (NSP4) is known to cause cell death by interacting with host protein(s) another NS protein, NSP1, determines the host range.Thus the objective of the proposed study is to initiate investigations into the molecular pathogenesis of RV to identify and characterize the host factors that interact with viral nonstructural proteins to establish their role in the viral replication/persistence and possible adverse reactions. Understanding the mechanism by which the host factors (proteins) determine rotaviral replication, host range and pathogenicity would help evaluating the safety and efficacy of rotaviral vaccines, as well as potential adverse reactions. Further, to address the possible adverse reactions following the public use of the candidate vaccines, there is a need for setting-up an infrastructure for the rotavirus research in our division (DVP). This would complement and enhance the lab-based review of RV vaccines for safety and efficacy.